Signal regulatory protein alpha (SIRPα) is a transmembrane protein belonging to the immunoglobulin superfamily, and a receptor for CD47. Cloning and expression of a human form of SIRPα has been described by Ullrich et al in U.S. Pat. No. 6,541,615. Involvement of SIRPα and CD47 in the etiology of cancer and other diseases has been implicated by Sarfati et al in WO1999/040940 and by Van den Berg et al in WO00/66159, who suggest therapeutic use of an inhibitor of SIRPα. More recently, Jaiswal et al have suggested the use of antibodies to CD47 for the treatment of hematopoietic cancers, in WO2009/091601. The interaction between SIRPα and CD47 plays an important role in regulating the phagocytosis of leukemia cells and leukemia stem cells (LSCs) by macrophages. Blocking antibodies against CD47 have been shown to promote phagocytosis of LSCs by macrophages. In addition, Wang et al have suggested cancer treatments based on SIRPα fusion proteins in WO 2010/130053. For treating immune disorders, Smith et al have suggested the use of CD47-based Fe fusions, in US2008/0131431. The treatment of inflammatory and immune disorders also is taught by Raymond et al, in WO2010/070047.
It would be useful to provide agents that inhibit signalling via the SIRPα/CD47 axis for use in the treatment of cancer and other diseases.